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    Columns

    ‘You Are What You Eat’ (Chapter 2): Nutrigenetics & Nutrigenomics

    Personalized approaches to nutrition intervention can benefit public health by pre-empting chronic and metabolic disease.

    ‘You Are What You Eat’ (Chapter 2): Nutrigenetics & Nutrigenomics
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    By Greg Stephens, Windrose Partners, and Sheila Campbell, PhD, RD06.02.22
    Our first memory of the axiom “You are what you eat” arises from our college days in the early 1970s. The saying meant that people need to eat good food to be fit and healthy. When the term was used, we usually referred to macrobiotic, organic whole foods.

    We also recall that later the phrase was applied in sports nutrition and used to admonish bodybuilders and other athletes to eat the right combination and amounts of nutrients to build muscle and achieve training goals. The simple application was: healthy food = healthy body.

    Reductionist Thinking Doesn’t Explain It

    In reductionist thinking, an issue can best be resolved by breaking it down to its components, then resolving each part. The fallacy is that in examining each piece, the bigger picture can be overlooked. As ancient philosopher Aristotle said: “the whole is greater than the sum of its parts.”

    His complete quotation is even more clear: “In the case of all things which have several parts and in which the totality is not, as it were, a mere heap, but the whole is something besides the parts, there is a cause; for even in bodies contact is the cause of unity in some cases, and in others viscosity or some other such quality.”1

    Scientific advances reveal that reductionist thinking about food and nutrition oversimplifies the complex ways that food, nutrients, and dietary compounds interact to shape us mentally and physically.

    You Are What You Eat: Chapter 2

    To us, completion of the Human Genome Project in 2003, evokes the same feeling of eerie awe as the star gate scene in the film “2001: A Space Odyssey.”

    The Human Genome Project was the 13-year international research effort to determine the DNA sequence of the entire human genome. We believe it provides a nearly metaphysical entry into the second chapter explaining “You are what you eat.” The mapping of the human genome has spawned new sciences, including nutrigenetics and nutrigenomics. 

    Nutrigenetics

    Nutrigenetics explains how genes and their constituent DNA affect the reaction to food and nutrients.

    Genes are made up of nucleotides (sequences of DNA). The differences in nucleotide composition (called alleles) produce variants that are responsible for differences in the genetic characteristics we express. Alleles can not only cause differences in eye color or hair texture; they also affect how we react to food
    and nutrients.

    An example that’s recently been in the news is the gene that provides instructions for making methylenetetrahydrofolate reductase (MTHFR). The MTHFR enzyme catalyzes the conversion of inactive folate to active folate. This form of folate is critical to converting the amino acid homocysteine (which can’t be used to create other proteins) to methionine, an amino acid that is needed to make other proteins. Two variants of the MTHFR gene exist. They are the C677T and the A1298C variants. When someone inherits one of each variant or two of the C677T, that person has higher risk of elevated homocysteine blood levels. Hyperhomocysteinemia can increase risk of cardiovascular disease.2

    It’s possible to order “do it yourself” genetic testing kits for the MTHFR gene for under $200. In an article titled, “A Genetic Test You Don’t Need,” geneticist Charis Eng said it’s easier and less costly to test blood levels of homocysteine and treat accordingly.3

    To summarize, nutrigenetics specifically investigates the effects of genetic inheritance in nutrition-related genes on micronutrient uptake and metabolism as well as dietary effects on health.

    Nutrigenomics

    Nutrigenomics studies the role of nutrients and bioactive dietary compounds on gene expression.

    A person’s genotype is the sum of their genetic inheritance. One’s physical characteristics, called their phenotype, result from expression of genes. Not all our genes are expressed.  Dominant variants of a gene are always expressed.

    Nutrients and general dietary patterns can regulate how and when genes are expressed. An example is the association between a high glycemic index (GI) diet and expression of the adiponectin gene. Adipose tissue secretes several adipokines, which influence metabolism. One of them, adiponectin, has antineoplastic, cardioprotective, and anti-inflammatory properties, and sensitizes tissues to insulin activity. 

    Studies demonstrate that high GI diets are associated with low adiponectin concentrations. It appears that these diets turn off adiponectin gene expression in turn increasing the risk of insulin resistance and hyperglycemia.4, 5

    We’re particularly interested in the ability of omega-3 fatty acids to regulate genes coding for inflammatory cytokines. In 1998, we were working at a large pharmaco-nutrition company when it commercialized an enteral tube feeding formula fortified with eicosapentaenoic acid (EPA) and gamma linoleic acid (GLA) and intended for critically ill patients with acute respiratory distress syndrome (ARDS).

    ARDS is a systemic inflammatory condition that is difficult to manage and associated with organ failure and significant mortality. Both EPA and GLA have anti-inflammatory properties. Early clinical studies showed that feeding the formula to patients with ARDS was associated with improved clinical outcomes and reductions in levels of inflammatory cytokines interleukin-6 (IL-6), a poor prognostic indicator in ARDS.6, 7, 8

    Results from later studies and meta-analyses were not as positive regarding effects of the formula on overall clinical outcomes.9

    However, animal studies demonstrate that certain fatty acids do effectively regulate inflammatory gene expression.10, 11

    Ordovas and associates cautioned: “Although much of the early ‘hype’ around nutrigenomics has not yet come to fruition, the field remains nascent and fast-moving, with the potential to lay the foundations of truly ‘personalised nutrition’ approaches tailored to individuals.”12

    In conclusion, we stand by our 2006 prediction: “The completion of the Human Genome Project is expected to greatly impact tube feeding specifically and nutrition care generally. This new science is expected to affect public health by allowing a personalized approach to nutrition intervention to ‘pre-empt’ chronic and metabolic disease.”13, 14

    About the Authors: Greg Stephens, RD, is president of Windrose Partners, a company serving clients in the the dietary supplement, functional food and natural product industries. Formerly vice president of strategic consulting with The Natural Marketing Institute (NMI) and Vice President of Sales and Marketing for Nurture, Inc (OatVantage), he has 25 years of specialized expertise in the nutritional and pharmaceutical industries. His prior experience includes a progressive series of senior management positions with Abbott Nutrition (Ross Products Division of Abbott Laboratories), including development of global nutrition strategies for disease-specific growth platforms and business development for Abbott’s medical foods portfolio. He can be reached at 267-432-2696; E-mail: gregstephens@windrosepartners.com. Sheila Campbell, PhD, RD, has practiced in the field of clinical nutrition for more than 30 years, including 17 years with Ross Products Division of Abbott Laboratories. She has authored more than 70 publications on scientific, clinical and medical topics and has presented 60 domestic and international lectures on health-related topics. She can be reached at smcampbellphdrd@gmail.com.

    References
    1. Aristotle. Aristotle’s Metaphysics, ed. W.D. Ross. Oxford: Clarendon Press. 1924.
    2. Ganguly, P., et al. (2015). Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6. doi: 10.1186/1475-2891-14-6
    3. Eng, C. (2020). A genetic test you don’t need. Health and Wellness Tips. Dec 16. https://health.clevelandclinic.org/a-genetic-test-you-dont-need/
    4. Torres-Castillo, N., et al. (2018). High Dietary ω-6:ω-3 PUFA Ratio Is Positively Associated with Excessive Adiposity and Waist Circumference. Obes. Facts. 2018;11:344–353. doi: 10.1159/000492116
    5. Pereira, R., et al. (2016). Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults. Int. J. Environ. Res. Public Health. 2016;13:54–63. doi: 10.3390/ijerph13010054
    6. Gadek, J. et al. (1999). Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group. Crit Care Med. 1999;27:1409–20. doi: 10.1097/00003246-199908000-00001
    7. Singer, P. et al. (2006). Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma linolenic acid in ventilated patients with acute lung injury. Crit Care Med. 2006;34:1033–8. doi: 10.1097/01.CCM.0000206111.23629.0A
    8. Pontes-Arruda, A. et al. (2006). Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med. 2006;34:2325–33. doi: 10.1097/01.CCM.0000234033.65657.B6
    9. Marik, P, et al. (2008). Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med. 2008;34:1980–90. doi: 10.1007/s00134-008-1213-6
    10. Ramalho, T. et al. (2020). Eicosapentaenoic Acid Regulates Inflammatory Pathways through Modulation of Transcripts and miRNA in Adipose Tissue of Obese Mice. Biomolecules. 2020 Sep 7;10(9):1292. doi: 10.3390/biom10091292
    11. Heshmati, J. (2021). Effect of omega-3 fatty acid supplementation on gene expression of inflammation, oxidative stress and cardiometabolic parameters: Systematic review and meta-analysis, Journal of Functional Foods, Volume 85, October 2021, 104619. doi: 10.1016/j.jff.2021.104619
    12. Ordovas, J., et al. (2018). Personalised nutrition and health. The British Medical Journal. Jun 13;361:bmj.k2173. doi: 10.1136/bmj.k2173
    13. Campbell, S. (2006). An Anthology of Advances in Enteral Tube Feeding Formulations. Nutrition in Clinical Practice: official publication of the American Society for Parenteral and Enteral Nutrition. 21. 411-5. doi: 10.1177/0115426506021004411.
    14. Fenech, M. et al. (2011). Nutrigenetics and nutrigenomics: viewpoints on the current status and applications in nutrition research and practice. J Nutrigenet Nutrigenomics. 2011;4(2):69-89. doi:10.1159/000327772
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